Establishment of a Transplantation Model of PDAC-Derived Liver Metastases.

BACKGROUND: The highly metastatic nature of pancreatic ductal adenocarcinoma (PDAC) and the difficulty to achieve favorable patient outcomes emphasize the need for novel therapeutic solutions. For preclinical evaluations, genetically engineered mouse models are often used to mimic human PDAC but frequently fail to replicate synchronous development and metastatic spread. This study aimed to develop a transplantation model to achieve synchronous and homogenous PDAC growth with controlled metastatic patterns in the liver. METHODS: To generate an orthotopic PDAC model, the DT6606 cell line was injected into the pancreas head of C57BL/6 mice, and their survival was monitored over time. To generate a heterotopic transplantation model, growing doses of three PDAC cell lines (DT6606, DT6606lm, and K8484) were injected into the portal vein of mice. Magnetic resonance imaging (MRI) was used to monitor metastatic progression, and histologic analysis was performed. RESULTS: Orthotopically injected mice succumbed to the tumor within an 11-week period (average survival time, 78.2 ± 4.45 days). Post-mortem examinations failed to identify liver metastasis. In the intraportal model, 2 × 105 DT6606 cells resulted in an absence of liver metastases by day 21, whereas 5 × 104 DT6606lm cells and 7 × 104 K8484 cells resulted in steady metastatic growth. Higher doses caused significant metastatic liver involvement. The use of K8484 cells ensured the growth of tumors closely resembling the histopathologic characteristics of human PDAC. CONCLUSIONS: This report details the authors' efforts to establish an "optimal" murine model for inducing metastatic PDAC, which is critical for advancing our understanding of the disease and developing more effective treatments.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (1) pre-transplant evaluation.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment in end-stage liver disease. Imaging is a key element for successful organ-transplantation to assist surgical planning. So far, only limited data regarding the best radiological approach to prepare children for liver transplantation is available. OBJECTIVES: In an attempt to harmonize imaging surrounding pediatric liver transplantation, the European Society of Pediatric Radiology (ESPR) Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phase. This paper reports the responses on preoperative imaging. MATERIAL AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted and 22 institutions from 11 countries returned the survey. From 2018 to 2020, the participating centers collectively conducted 1,524 transplantations, with a median of 20 transplantations per center per annum (range, 8-60). RESULTS: Most sites (64%) consider ultrasound their preferred modality to define anatomy and to plan surgery in children before liver transplantation, and additional cross-sectional imaging is only used to answer specific questions (computed tomography [CT], 90.9%; magnetic resonance imaging [MRI], 54.5%). One-third of centers (31.8%) rely primarily on CT for pre-transplant evaluation. Imaging protocols differed substantially regarding applied CT scan ranges, number of contrast phases (range 1-4 phases), and applied MRI techniques. CONCLUSION: Diagnostic imaging is generally used in the work-up of children before liver transplantation. Substantial differences were noted regarding choice of modalities and protocols. We have identified starting points for future optimization and harmonization of the imaging approach to multicenter studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (3) postoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of postoperative complications. So far, limited data is available regarding the best radiologic approach to monitor children after liver transplantation. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra-, and postoperative phases. This paper reports the responses related to postoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: All sites commence ultrasound (US) monitoring within 24 h after liver transplantation. Monitoring frequency varies across sites, ranging from every 8 h to 72 h in early, and from daily to sporadic use in late postoperative phases. Predefined US protocols are used by 73% of sites. This commonly includes gray scale, color Doppler, and quantitative flow assessment. Alternative flow imaging techniques, contrast-enhanced US, and elastography are applied at 31.8%, 18.2%, and 63.6% of sites, respectively. Computed tomography is performed at 86.4% of sites when clarification is needed. Magnetic resonance imaging is used for selected cases at 36.4% of sites, mainly for assessment of biliary abnormalities or when blood tests are abnormal. CONCLUSION: Diagnostic imaging is extensively used for postoperative surveillance of children after liver transplantation. While US is generally prioritized, substantial differences were noted in US protocol, timing, and monitoring frequency. The study highlights potential areas for future optimization and standardization of imaging, essential for conducting multicenter studies.

European Society of Pediatric Radiology survey of perioperative imaging in pediatric liver transplantation: (2) intraoperative imaging.

BACKGROUND: Liver transplantation is the state-of-the-art curative treatment for end-stage liver disease. Imaging is a key element in the detection of intraoperative and postoperative complications. So far, only limited data regarding the best radiological approach to monitor children during liver transplantation is available. OBJECTIVE: To harmonize the imaging of pediatric liver transplantation, the European Society of Pediatric Radiology Abdominal Taskforce initiated a survey addressing the current status of imaging including the pre-, intra- and postoperative phase. This paper reports the responses related to intraoperative imaging. MATERIALS AND METHODS: An online survey, initiated in 2021, asked European centers performing pediatric liver transplantation 48 questions about their imaging approach. In total, 26 centers were contacted, and 22 institutions from 11 countries returned the survey. RESULTS: Intraoperative ultrasound (US) is used by all sites to assess the quality of the vascular anastomosis in order to ensure optimal perfusion of the liver transplant. Vessel depiction is commonly achieved using color Doppler (95.3%). Additional US-based techniques are employed by fewer centers (power angio mode, 28.6%; B-flow, 19%; contrast-enhanced US, 14.3%). Most centers prefer a collaborative approach, with surgeons responsible for probe handling, while radiologists operate the US machine (47.6%). Less commonly, the intraoperative US is performed by the surgeon alone (28.6%) or by the radiologist alone (23.8%). Timing of US, imaging frequency, and documentation practices vary among centers. CONCLUSION: Intraoperative US is consistently utilized across all sites during pediatric liver transplantation. However, considerable variations were observed in terms of the US setup, technique preferences, timing of controls, and documentation practices. These differences provide valuable insights for future optimization and harmonization studies.

Venous outflow obstruction in pediatric left lateral segment split liver transplantation.

BACKGROUND: Venous outflow obstruction (VOO) is a known cause of graft and patient loss after pediatric liver transplantation (LT). We analyzed the incidence, risk factors, diagnosis, management, and outcome of VOO in a large, consecutive series of left lateral segment (LLS) split LT with end-to-side triangular venous anastomosis. METHODS: We evaluated data collected in our prospective databases relative to all consecutive pediatric liver transplants performed from January 2006 to December 2021. We included in this study children undergoing LLS split liver transplant with end-to-side triangular anastomosis. Diagnosis of VOO was based on clinical suspicion and radiological confirmation. RESULTS: VOO occurred in 24/279 transplants (8.6%), and it was associated with lower graft weight (p = .04), re-transplantation (p = .008), and presence of two hepatic veins (p < .0001). In presence of two segmental veins' orifices, the type of reconstruction (single anastomosis after venoplasty or double anastomosis) was not significantly related to VOO (p = .87). Multivariable analysis indicated VOO as a risk factor for graft lost (hazard ratio 3.21, 95% confidence interval 1.22-8.46; p = .01). Percutaneous Transluminal Angioplasty (PTA) was effective in 17/22 (77%) transplants. Surgical anastomosis was redone in one case. Overall six grafts (25%) were lost. CONCLUSION: VOO after LLS split LT with end-to-side triangular anastomosis is an unusual but critical complication leading to graft loss in a quarter of cases. The occurrence of VOO was associated with lower graft weight, re-transplantation, and presence of two hepatic veins. PTA was safe and effective to restore proper venous outflow in most cases.

CT renal arteriography as a novel imaging guidance for the percutaneous ablation of small renal tumors.

PURPOSE: To report procedural data and outcomes of a novel image guidance technique, CT renal arteriography (CTRA), performed to target and ablate small intraparenchymal renal tumors. MATERIALS AND METHODS: We retrospectively analyzed data of 2 patients undergoing CTRA-guided ablation for 3 renal intraparenchymal tumors, from February to March 2023. We previously evaluated tumor visibility with US/CEUS, and in all cases conspicuity was poor, whereas contrast-enhanced CT (CECT) clearly depicted all hypervascular nodules. Our primary endpoint was CTRA-guidance feasibility for renal ablation, defined as the precise probe deployment inside the target tumor. The secondary endpoint was CTRA-guided ablation technical success, intended as the inclusion of the whole tumor inside the necrotic volume, with 5 mm safety margins. RENAL scores, complications, procedural time, dose length product (DLP), serum creatinine variation and hospital stay length were also recorded. RESULTS: A confident deployment of the probe tip inside the nodule was accomplished in all 3 cases, with a 100% of correct targeting. We observed immediate technical success after all 3 ablations. The 3 nodules had a RENAL score <7 points, and we encountered no complications due to line placement or ablation. The average time from preablative to postablative CTRA was 54 min (50-58min), with a DLP of 3632mGy*cm (2807-4458mGy*cm). Serum creatinine didn't show a significant variation after the procedures; both patients were hospitalized for 2 days. CONCLUSION: Preliminary data showed that CTRA-guidance might provide unique advantages over conventional CECT-guidance to assist the ablation of small renal intraparenchymal tumor not visualized on US/CEUS.

US-guided percutaneous thrombin injection to treat non-femoral artery pseudoaneurysms: preliminary experience and review of the literature.

PURPOSE: To evaluate the clinical outcome of US-guided percutaneous thrombin injection in the treatment of non-femoral artery pseudoaneurysms (NFAP). MATERIALS AND METHODS: Among all pseudoaneurysms treated in our institution, we retrospectively collected NFAP embolized with percutaneous thrombin injections from January 1, 2015, to December 31, 2021. The embolization was prompted for an ongoing antiaggregating/anticoagulation therapy, NFAP optimal US visibility, or high surgery-related risks. Causes, location, size and neck of NFAP, complications, number of repeated treatments, clinical success and patients clinical conditions at discharge were annotated. The endpoint for clinical success was the resolution of NFAP at postprocedural imaging, with no resort to surgery. RESULTS: Eight consecutive patients (5 females, median age 73 years, range 46-84) underwent 16 procedures. Arterial damage was due to catheterization (3), CVC mispositioning (2), trauma, hemorrhagic diathesis and endoprosthesis endoleak. We treated humeral (2), subclavian (2), thyrocervical, anterior tibial, radial and pancreaticoduodenal arteries. Median pseudoaneurysm size was 530 mm2 (range 32-2400 mm2), with a thin (7/8) or non-visible (1/8) neck. No complications occurred. Clinical success was obtained in 7/8 patients (88%), with a single treatment in 4, multiple in 3 cases (4 embolizations, 3 and 2, respectively). One patient underwent surgical suture after the second failed attempt of percutaneous embolization. Seven patients were discharged in good clinical conditions; one died during hospitalization, due to the worsening of the underlying cardiac disease. CONCLUSIONS: Percutaneous US-guided thrombin injection to treat NFAP is feasible in selected cases, with rare complications. Clinical success is often reached, also by repeated injections.

RAB39B-mediated trafficking of the GluA2-AMPAR subunit controls dendritic spine maturation and intellectual disability-related behaviour.

Mutations in the RAB39B gene cause X-linked intellectual disability (XLID), comorbid with autism spectrum disorders or early Parkinson's disease. One of the functions of the neuronal small GTPase RAB39B is to drive GluA2/GluA3 α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) maturation and trafficking, determining AMPAR subunit composition at glutamatergic postsynaptic neuronal terminals. Taking advantage of the Rab39b knockout murine model, we show that a lack of RAB39B affects neuronal dendritic spine refinement, prompting a more Ca2+-permeable and excitable synaptic network, which correlates with an immature spine arrangement and behavioural and cognitive alterations in adult mice. The persistence of immature circuits is triggered by increased hypermobility of the spine, which is restored by the Ca2+-permeable AMPAR antagonist NASPM. Together, these data confirm that RAB39B controls AMPAR trafficking, which in turn plays a pivotal role in neuronal dendritic spine remodelling and that targeting Ca2+-permeable AMPARs may highlight future pharmaceutical interventions for RAB39B-associated disease conditions.

Biliary complications in pediatric liver transplantation: findings of percutaneous transhepatic cholangiography in a large single-center cohort.

BACKGROUND: Although biliary complications after orthotopic liver transplantation represent a common source of morbidity and mortality, decreasing graft survival, consensus is lacking on their management in the pediatric population. OBJECTIVE: The aim of this study was to present the prevalence of such biliary complications and their interventional radiologic management with representative images. MATERIALS AND METHODS: This retrospective study reports our experience with percutaneous transhepatic cholangiography in the management of biliary complications after orthotopic liver transplantation in pediatric patients. This study enrolled all pediatric patients (<18 years old) who underwent percutaneous transhepatic cholangiography for the management of biliary complications after orthotopic liver transplantation at a tertiary care center between January 2010 and December 2020. Diagnosis of biliary complications and indication to perform percutaneous transhepatic cholangiography were based on clinical, laboratory or radiologic data. RESULTS: Among the 301 orthotopic liver transplantations, 78 (26%) developed biliary complications that were managed by interventional radiology: these included 52 (17.3%) biliary strictures, 19 (6.3%) bile leaks, 5 (1.7%) biliary stones, 1 (0.3%) iatrogenic biliary obstruction and 1 (0.3%) vanishing syndrome. The median time interval between orthotopic liver transplantation and the diagnosis of biliary complications was 6.0 years (interquartile range [IQR] 8.2 years). Percutaneous transhepatic cholangiography and biliary duct catheterization were successful in all cases, with low rates of complications that were variable among subgroups. CONCLUSION: A wide spectrum of biliary complications can occur after pediatric orthotopic liver transplantation. In this large single-center experience, we highlight the value of percutaneous transhepatic cholangiography in their diagnosis and management. Percutaneous treatments in pediatric patients are safe and effective, providing resolution or serving as a bridge to surgery, including re-transplantation.

Primary non-parasitic splenic cyst: US- and fluoroscopy-guided percutaneous management by alcohol sclerosis on six patients.

PURPOSE: This manuscript aims to report on a retrospective analysis of six patients treated with combined US- and fluoroscopic-guided percutaneous alcohol sclerosis for primary non-parasitic splenic cysts. METHODS: In this retrospective analysis, three females and three males affected by primary non-parasitic splenic cysts were included. All except one were symptomatic. Preoperative cyst diameter was in mean 113 mm (range: 67-210 mm). Ethanol 96% was adopted as sclerosant agent; the amount of ethanol injected corresponded to the 20%-30% of the cystic volume. US follow-up was planned at 2/4 weeks; MR follow-up was conducted almost at 6 months after the last treatment session. Technical success was considered as cyst disappearance or reduction of the maximum diameter <50 mm; clinical success, in those symptomatic cases, was considered as symptoms resolution or marked improvement. RESULTS: Eleven procedures had been performed: one in three patients, three in two patients and two in one patient. Technical success was 83.3%; clinical success was 80%. Only one patient, with a preoperative cystic diameter of 210 mm and despite three treatment sessions, had an increase in the cystic size and did not report symptoms improvement. CONCLUSIONS: In this sample, US-guided percutaneous alcohol sclerosis was a safe and effective spleen preserving option to treat primary non-parasitic splenic cysts.

Multimodality imaging in acute myocarditis.

The diagnosis of acute myocarditis often involves several noninvasive techniques that can provide information regarding volumes, ejection fraction, and tissue characterization. In particular, echocardiography is extremely helpful for the evaluation of biventricular volumes, strain and ejection fraction. Cardiac magnetic resonance, beyond biventricular volumes, strain, and ejection fraction allows to characterize myocardial tissue providing information regarding edema, hyperemia, and fibrosis. Contemporary cardiac computed tomography angiography (CCTA) can not only be extremely important for the assessment of coronary arteries, pulmonary arteries and aorta but also tissue characterization using CCTA can be an additional tool that can explain chest pain with a diagnosis of myocarditis.

IVC filter retrieval: a multicenter proposal of two score systems to predict application of complex technique and procedural outcome.

PURPOSE: Aim of this study was to identify preprocedural parameters, which may predict the application of a complex IVC filter retrieval technique and estimate the procedural outcome by applying two dedicated score systems. MATERIALS AND METHODS: In this retrospective multicenter analysis, data concerning patient, filter and procedure characteristics were retrieved from January 2018 to March 2020. Patients were evaluated according to the retrieval technique (standard vs. complex) and the procedural outcome (success vs. failure). Significant differences among these groups were evaluated, and two score systems were developed to predict the application of a complex retrieval technique and the procedural outcome. RESULTS: One hundred and sixteen IVC filters were retrieved in 116 patients. In 98 subjects, the filter was retrieved with a standard procedure (Standard group, 84.5% vs. Complex group, 15.5%), while in 106 patients the procedure was successful (Success group, 91.4% vs. Failure group, 8.6%). Statistically significant differences were noted in terms of embedded filter hook, filter apex tilt, angle between filter axis and IVC, caval wall penetration, dwelling time and procedural time. Two score 0-5 points to predict the need for a complex retrieval technique and the procedural outcome were developed, with a prognostic accuracy of 88.8% and 91.4%, respectively. CONCLUSION: Significant differences were appreciable analyzing the sample data comparing both the retrieval technique applied and the procedural outcome. Two predictive scores were developed to assess the need for applying a complex retrieval technique and to estimate the procedural outcome.

Elective Embolization of Splenic Artery Aneurysms with an Ethylene Vinyl Alcohol Copolymer Agent (Squid) and Detachable Coils.

PURPOSE: To report the safety and efficacy of the embolization of splenic artery aneurysms (SAAs) with coils plus ethylene vinyl alcohol copolymer (EVOH) agent. MATERIALS AND METHODS: A single-center retrospective study was conducted from 2016 to 2019 to collect SAAs. Twelve asymptomatic patients (mean age, 59 years) with 15 SAAs (mean size, 23.6 mm; size range, 15-40 mm) were treated with embolization. Embolization was performed with EVOH (Squid 8/34) and fibered detachable coils. Transfemoral embolization was performed with a microcatheter to achieve a splenic artery occlusion embolizing the SAA and its efferent and afferent branches. Follow-up was based on color Doppler ultrasound at 24 hours and on computed tomography (CT) angiography at 1 (n = 12) and 6 months (n = 12) after embolization. Mean number of coils and Squid vials used for each patient, major/minor complications, technical success, 30-day clinical success, cases of revascularization/reintervention, and mortality were assessed. Technical success was defined as complete exclusion of the aneurysmal segment and cessation of blood flow into the sac. Clinical success at 1 month was based on the absence of clinical symptoms and the exclusion of aneurysm revascularization on CT angiography. RESULTS: The mean number of coils and Squid vials was 5.75 (standard deviation [SD], 1.58; range, 3-9) and 1.41 (SD, 0.49; range, 1-2), respectively. Both technical and 30-day clinical success were 100%, with no cases of aneurysm revascularization (CT angiography performed in all patients at 1 month and 6 months and in 3 patients at 24 months). No major complications or fatal events were recorded. In terms of minor complications, 2 cases of mild pancreatitis (transient amylases increase) and 1 case of focal splenic ischemia without clinical sequelae were recorded. CONCLUSIONS: Embolization in SAAs using coils plus EVOH was safe and effective without SAA revascularization.

Comparison between percutaneous and laparoscopic microwave ablation of hepatocellular carcinoma.

Background: Based on patient and tumor characteristics, some authors favor laparoscopic microwave ablation (LMWA) over the percutaneous approach (PMWA) for treatment of hepatocellular carcinoma (HCC). We compared the two techniques in terms of technique efficacy, local tumor progression (LTP) and complication rates.Study design: A retrospective comparative analysis was performed on 91 consecutive patients (102 HCC tumors) who underwent PMWA or LMWA between October 2014 and May 2019. Technique efficacy at one-month and LTP at follow-up were assessed by contrast-enhanced CT/MRI. Kaplan-Meier estimates and Cox regression were used to compare LTP-free survival (LTPFS).Results: At baseline analysis, LMWA group showed higher frequency of multinodular disease (p < .001) and average higher energy delivered over tumor size (p = .033); PMWA group showed higher rates of non-treatment-naïve patients (p = .001), patients with Hepatitis-C (p = .03) and BCLC-A1 disease (p = .006). Technique efficacy was not significantly different between the two groups (p = .18). Among effectively treated patients, 75 (83 tumors) satisfied ≥6 months follow-up, 54 (57 tumors) undergoing PMWA and 21 (26 tumors) LMWA. LTP occurred in 14/83 cases (16.9%): 12 after PMWA (21.1%) and 2 after LMWA (7.7%). At univariate analysis, technique did not correlate to LTPFS (p = .28). Subgroup analysis showed a trend toward worse LTPFS after PMWA of subcapsular tumors (p = .16). Major complications were observed in six patients (6.6%), 2 after PMWA and 4 after LMWA (3.2% vs 14.3%, p = .049).Conclusions: Technical approach did not affect LTPFS. Complications were reported more frequently after LMWA. Despite higher complication rates, LMWA seems a valid option for treatment of subcapsular tumors.

Four-class tumor staging for early diagnosis and monitoring of murine pancreatic cancer using magnetic resonance and ultrasound.

Background: The widely used genetically engineered mouse LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre, termed KPC, spontaneously develops pancreatic cancer mirroring all phases of the carcinogenesis but in asynchronous manner. Preclinical studies need defined criteria for the enrollment of the KPC sharing the same stage of carcinogenesis. Aim: To define a tumor-staging criteria using magnetic resonance (MR) and ultrasound (US) and then to correlate the imaging stage with overall survival of KPC mice. Methods: Forty KPC (2- to 5-month-old mice) were imaged by axial fat-saturated T2-weighted sequences at MR and by brightness mode US to establish criteria for tumor staging. Immunohistopathology was used to validate imaging. A second cohort of 25 KPC was used to correlate imaging stage with survival by Kaplan-Meier analysis. Results: We defined a four-class tumor staging system ranking from stages 1 to 4. Stage 1 was described as radiologically healthy pancreas; precursor lesions were detectable in histology only. Cystic papillary neoplasms, besides other premalignant alterations, marked stage 2 in the absence of cancer nodules. Stages 3 and 4 identified mice affected by overt pancreatic cancer with size <5 or ≥5 mm, respectively. Regarding the prognosis, this staging system correlated with disease-related mortality whatever may be the KPC age when they staged. Conclusion: This imaging-based four-class tumor staging is an effective and safe method to stage pancreatic cancer development in KPC. As a result, regardless of their age, KPC mice can be synchronized based on prognosis or on a specific phase of tumorigenesis, such as the early but already radiologically detectable one (stage 2).

Covered stenting and transcatheter embolization of splenic artery aneurysms in diabetic patients: A review of endovascular treatment of visceral artery aneurysms in the current era.

Diabetes mellitus is associated with both microvascular and macrovascular complications, which can result in visceral aneurysms as for example splenic artery aneurysms: in their management, an endovascular treatment, less invasive than surgery, is generally preferred. Endovascular treatment of splenic artery aneurysms can be based either on covered stenting (CS) or transcatheter embolization (TE). CS generally allows aneurysm exclusion with vessel preservation, while TE usually determines target artery occlusion with potential risk of distal ischemia. We performed a review of the existing literature on endovascular treatment of visceral artery aneurysms (VAAs) and psudoaneurysms (VAPAs) in the current era.